Department of Genetics, Cancer Research Institute, Biomedical Research Center of the Slovak Academy of Sciences, Dubravska cesta 9, 845 05 Bratislava, Slovakia.
Institute of Pathological Physiology, Faculty of Medicine, Comenius University, Sasinkova 4, 811 08 Bratislava, Slovakia.
Int J Mol Sci. 2023 Dec 6;24(24):17199. doi: 10.3390/ijms242417199.
Cancer cell dissemination involves invasion, migration, resistance to stressors in the circulation, extravasation, colonization, and other functions responsible for macroscopic metastases. By enhancing invasiveness, motility, and intravasation, the epithelial-to-mesenchymal transition (EMT) process promotes the generation of circulating tumor cells and their collective migration. Preclinical and clinical studies have documented intensive crosstalk between the gut microbiome, host organism, and immune system. According to the findings, polymorphic microbes might play diverse roles in tumorigenesis, cancer progression, and therapy response. Microbial imbalances and changes in the levels of bacterial metabolites and toxins promote cancer progression via EMT and angiogenesis. In contrast, a favorable microbial composition, together with microbiota-derived metabolites, such as short-chain fatty acids (SCFAs), can attenuate the processes of tumor initiation, disease progression, and the formation of distant metastases. In this review, we highlight the role of the intratumoral and gut microbiomes in cancer cell invasion, migration, and metastatic ability and outline the potential options for microbiota modulation. As shown in murine models, probiotics inhibited tumor development, reduced tumor volume, and suppressed angiogenesis and metastasis. Moreover, modulation of an unfavorable microbiome might improve efficacy and reduce treatment-related toxicities, bringing clinical benefit to patients with metastatic cancer.
癌细胞的扩散涉及浸润、迁移、抵抗循环中的应激物、渗出、定植以及其他负责宏观转移的功能。上皮-间质转化(EMT)过程通过增强侵袭性、迁移性和血管内渗能力,促进循环肿瘤细胞的产生及其集体迁移。临床前和临床研究记录了肠道微生物组、宿主生物体和免疫系统之间的密集串扰。根据这些发现,多态微生物可能在肿瘤发生、癌症进展和治疗反应中发挥不同的作用。微生物失衡和细菌代谢物和毒素水平的变化通过 EMT 和血管生成促进癌症进展。相比之下,有利的微生物组成以及微生物衍生的代谢物,如短链脂肪酸(SCFAs),可以减弱肿瘤起始、疾病进展和远处转移的形成过程。在这篇综述中,我们强调了肿瘤内和肠道微生物组在癌细胞浸润、迁移和转移能力中的作用,并概述了调节微生物组的潜在选择。正如在小鼠模型中所显示的那样,益生菌抑制了肿瘤的发展,减少了肿瘤体积,并抑制了血管生成和转移。此外,调节不利的微生物组可能会提高疗效并降低与治疗相关的毒性,为转移性癌症患者带来临床益处。
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